Updates to Good Manufacturing PracticesRecent, current and future changes

Matt DavisSenior InspectorManufacturing Quality Branch

August 2019

OverviewUpdates to TGA Guidance

Adoption of PE009-14

Changes in version 14

Future updates to the PIC/S GMPs

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Updates to TGA Guidance

• PE009-13, the PIC/S guide to GMP for medicinal products: TGA interpretation and expectations for demonstrating compliance

• Release for supply of medicines

General GMP Guidance

• Ongoing stability testing for listed and complementary medicines• Process validation for listed and complementary medicines• Product Quality Reviews (PQRs) for listed and complementary medicines• Sampling and testing for listed and complementary medicines• Supplier assessment, approval and qualification for listed and complementary

medicines

Listed & Complementary Medicines

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Updates to TGA Guidance

• Sunscreen manufacturing: demonstrating compliance with the PIC/S Guide to GMP PE009-13

• Manufacture of sterile radiopharmaceuticals labelled with fluorine-18 • Manufacture of medicinal cannabis for supply under 'approved access' provisions• Medicinal gases and good manufacturing practice (GMP)

Specific Dosage forms

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MQB Adoption Timeline for PE009-14

April 2019 - 3 Months•Gap Analysis TIWGG

•Notification for industry•Main changes table•Adoption strategy•Deficiency reporting

DD MMM 202?•Adopt New GMP Guide

•Publish Q&A for GMP

+6 months + 12 months Ongoing

12m Transition Period

Assess & establish Implement Full Compliance

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TIWGG Members:AccordAustralia New Zealand Industrial Gas Association (ANZIGA)Active Pharmaceutical Ingredient Manufacturer's Association of Australia (APIMAA)Complementary Medicines Australia (CMA)Consumer Healthcare Products Australia (formerly ASMI) Generic and Biosimilar Medicines Association (GBMA)Medicines Australia (MA).

PE009-14 Chapter 3 – Premises and Equipment• Additional guidance on Cross-contamination• Quality Risk Management principles should be used to

assess and control the risks.• Dedicated facilities are required when:

– the risk cannot be adequately controlled by operational and/ or technical measures,

– scientific data from the toxicological evaluation does not support a controllable risk (e.g. allergenic potential from highly sensitising materials such as beta-lactams) or

– relevant residue limits, derived from the toxicological evaluation, cannot be satisfactorily determined by a validated analytical method.

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PE009-14 Chapter 5 – Production – Cross Contamination (1)• Quality Risk Management process… should be used to assess and

control the cross-contamination risks presented by the products manufactured.

• Technical Measures:– Dedicated processes, equipment and facilities;– Use of closed systems, barrier, isolator, single-use technologies;– Dust extraction, air-locks, pressure cascades;– Clean-in-place, ease of cleaning considered in process/equipment

design • Organisational Measures:

– Campaign operation, campaign washing, cleaning verification;– Gown management, waste management, spill management;– Detailed cleaning records and instructions, continued oversight of

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PE009-14 Chapter 5 – Production – Starting Materials • Selection, qualification, approval and maintenance of suppliers of starting materials, together with

their purchase and acceptance, should be documented as part of the pharmaceutical quality system.• Staff involved in these activities should have a current knowledge of the suppliers, the supply chain and

the associated risks involved. • Active Substances

– Supply chain traceability established and associated risks formally assessed and periodically verified.

– Audits should be carried out at the manufacturers and distributors of active substances…audits should be of an appropriate duration and scope to ensure that a full and clear assessment of GMP is made.

– The holder of the manufacturing authorisation shall verify such compliance either by himself/herself or through an entity acting on his/her behalf under a contract.

• Excipients – formalised quality risk assessment (PI 045-1)

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PE009-14 Chapter 8 – Complaints & Product Recall• Defined requirements for Personnel and Organisation within the PQS

• Procedures for handling and investigating complaints including possible

quality defects

• Investigation and decision making

• Root cause analysis and CAPA

• Product Recalls and risk-reducing actions

• Reflects URPTG requirements

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PE009-14 Annex 17– RTRT & Parametric Release• Real Time Release Testing (RTRT) (ICH Q8 Q&A)• Control of critical parameters and relevant material attributes are

authorised as an alternative to routine end-product testing of active substances and/or finished products.

• RTRT may apply to any stage in the manufacturing process and to any type of finished products or active substances, including their intermediates.

• Real time measurement of CPP(s) as a predictor of compliance with CQA.

• Thorough understanding of critical material attributes.• Well defined control strategy: QRM, validation, change control,

training, etc

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PE009-14 Annex 17– RTRT & Parametric Release• Parametric Release – terminally sterilised products

• Updates to text providing clarification of existing requirements.

• Detailed guidance regarding the scope of the sterility assurance program.

• Additional emphasis on Quality Risk Management.

• Guidance for pre-sterilisation bioburden testing and controls, and consideration of heat-resistant organisms.

• Well defined control strategy: QRM, validation, change control, training, etc

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Future PIC/S GMP UpdatesAnnex 1 – Sterile

Medicinal Products

Annex 2A/2B - Advanced Therapy Medicinal

Products & Biological substances and products

Annex 11 ComputerisedSystems & Chapter 4

Annex 13 –Investigational Medicinal

Products

Annex 16 - Certification by the Authorised Person

and Batch Release

Annex 21 – Importation

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Summary• TGA Guidance documents available on TGA website• TGA has commenced reviews of PE009-14 and will continue to work with industry

on adoption of future changes• Several changes in the pipeline• Get involved!

– EMA/EC Feedback– TGA/TIWGG Feedback

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